ALLSCHWIL, Switzerland I May 8, 2013 I Actelion Ltd (SIX: ATLN) announced today that the Independent Data Monitoring Committee (DMC) has informed the company of its unanimous recommendation to continue the pivotal Phase III study, GRIPHON. In addition the DMC had no recommendations for any modification in study design or procedures.
The placebo-controlled, randomized GRIPHON study is designed to evaluate the efficacy and safety of selexipag in 1’150 patients with pulmonary arterial hypertension (PAH) in an event-driven morbidity/mortality study.
Selexipag is an orally available selective IP receptor agonist that – in a Phase II study – showed a significant reduction in pulmonary vascular resistance (PVR). Pulmonary arterial hypertension (PAH) is a syndrome characterized by a progressive increase in pulmonary vascular resistance.
As described in the study protocol, the GRIPHON DMC was scheduled to perform an interim analysis at around two thirds of the overall foreseen morbidity/mortality events were observed, in addition to the evaluation of patient safety in the study. The goal of the interim analysis was to assess whether study continuation was warranted based on the primary objective of demonstrating morbidity/mortality benefits.
With the interim analysis now successfully concluded and the DMC recommending study continuation as planned, final study results of this event-driven study are now expected by mid-2014.
###
Notes to Editor:
ABOUT GRIPHON
GRIPHON, (Prostacyclin (PGI2) Receptor agonist in pulmonary arterial hypertension) is a multicenter, double-blind, placebo-controlled trial evaluating the long-term efficacy and safety of oral selexipag in patients with pulmonary arterial hypertension.
GRIPHON is close to full enrollment with 1’143 patients randomized, of the targeted 1’150, and represents the largest randomized, controlled study in PAH patients. This pivotal study is designed to demonstrate a reduction in risk of morbidity/mortality events of selexipag treatment compared to placebo and evaluate the safety of the selexipag in PAH patients. Results are expected to be available mid-2014.
ABOUT SELEXIPAG
Selexipag, originally discovered and synthesized by Nippon Shinyaku, is a first-in-class, potent, orally available, selective IP receptor agonist. Selexipag has major potential as a novel treatment of pulmonary arterial hypertension.[1,2,4]
Results of a Phase II, 43-patient, placebo-controlled, double-blind study, where patients were randomized in a 3:1 ratio receiving selexipag or placebo on top of PDE5 and/or ERA, showed a statistically significant reduction in pulmonary vascular resistance (PVR; primary parameter for the study). The treatment effect was shown to be 30.3% after 17 weeks of treatment (p=0.0045). Results also showed an encouraging numerical improvement in 6-minute walk distance (6MWD), which was a secondary endpoint of this trial. Selexipag was well tolerated and the safety profile was in-line with the expected pharmacologic effect. [3]
ABOUT PULMONARY ARTERIAL HYPERTENSION (PAH)
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The symptoms of PAH are non-specific and can range from mild breathlessness and fatigue during normal daily activity to symptoms of right heart failure and severe restrictions on exercise capacity and ultimately reduced life expectancy.
PAH is one group within the classification of pulmonary hypertension (PH). This group includes idiopathic PAH, heritable PAH and PAH caused by factors which include connective tissue disease, HIV infection and congenital heart disease.
The last decade has seen significant advances in the understanding of the pathophysiology of PAH, which has been paralleled with developments of treatment guidelines and new therapies. Drugs targeting the 3 pathways that have been established in the pathogenesis of PAH are endothelin receptor antagonists (ERAs), prostacyclins and phosphodiesterase-5 inhibitors. PAH treatments have transformed the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago to delayed disease progression today. Improved disease awareness and evidence-based guidelines developed from randomized controlled clinical trial data have highlighted the need for early intervention, goal-oriented treatment and combination therapy.
Despite these advances in PAH, survival rates are unacceptably low and PAH remains incurable.
ABOUT PROSTACYCLIN
Prostacyclin and prostaglandins are types of prostanoids. Endothelial cells produce several vasoactive chemical factors, among them prostacyclin (PGI2), which induce vasodilation of blood vessels and inhibit smooth muscle cell proliferation and platelet aggregation. The peptide endothelin is also produced by the endothelium, and is a potent constrictor of blood vessels and promotes cell proliferation. In a normal healthy state, prostacyclin helps counter-balance the actions of endothelin. In certain disease conditions, however, production of prostacyclin by the endothelium is impaired, allowing the deleterious effects of excessive levels of endothelin to predominate.
ABOUT PROSTACYCLIN RECEPTOR AGONISM
The IP receptor (PGI2 (prostacyclin) receptor) is one of 5 types of prostanoid receptor available to prostanoid replacement therapies. Prostacyclin activates the IP receptor inducing vasodilation and inhibiting proliferation of vascular smooth muscle cells. With selective IP receptor agonism, the risk of side effects mediated by activation of other prostanoid receptors may be minimized.
Actelion is developing a first-in-class, orally available, selective IP receptor agonist that mimics the actions of endogenous prostacyclin for the treatment of PAH.
ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE
Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance in April 2008 to collaborate on selexipag, a first-in-class orally-available, selective IP receptor agonist for patients suffering from pulmonary arterial hypertension (PAH). This compound was originally discovered and synthesized by Nippon Shinyaku. Phase II evaluation has been completed, and a Phase III program in PAH patients has been initiated. Actelion is responsible for global development and commercialization of selexipag outside Japan, while the two companies will co-develop and co-commercialize in Japan. Nippon Shinyaku will receive milestone payments based on development stage and sales milestones as well as royalties on any sales of selexipag.
References
- Kuwano et al. NS-304, an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 2007;322:1181-1188.
- Kuwano et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, NS-304, ameliorates rat pulmonary hypertension with unique relaxant responses of its active form MRE-269 on rat pulmonary artery. J Pharmacol Exp Ther 2008;326:691-699.
- Simonneau G, Lang I, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N. Selexipag, an oral, selective IP receptor agonist for the treatment of pulmonary arterial hypertension Eur Respir J 2012; 40: 874-880
- Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.
NIPPON SHINYAKU
For further information on Nippon Shinyaku please visit:
http://www.nippon-shinyaku.co.jp/english/index.html
ACTELION LTD
Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion’s first drug Tracleer®, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer® through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan, Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium – the single layer of cells separating every blood vessel from the blood stream. Actelion’s over 2,300 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI®).
SOURCE: Actelion
Post Views: 296
ALLSCHWIL, Switzerland I May 8, 2013 I Actelion Ltd (SIX: ATLN) announced today that the Independent Data Monitoring Committee (DMC) has informed the company of its unanimous recommendation to continue the pivotal Phase III study, GRIPHON. In addition the DMC had no recommendations for any modification in study design or procedures.
The placebo-controlled, randomized GRIPHON study is designed to evaluate the efficacy and safety of selexipag in 1’150 patients with pulmonary arterial hypertension (PAH) in an event-driven morbidity/mortality study.
Selexipag is an orally available selective IP receptor agonist that – in a Phase II study – showed a significant reduction in pulmonary vascular resistance (PVR). Pulmonary arterial hypertension (PAH) is a syndrome characterized by a progressive increase in pulmonary vascular resistance.
As described in the study protocol, the GRIPHON DMC was scheduled to perform an interim analysis at around two thirds of the overall foreseen morbidity/mortality events were observed, in addition to the evaluation of patient safety in the study. The goal of the interim analysis was to assess whether study continuation was warranted based on the primary objective of demonstrating morbidity/mortality benefits.
With the interim analysis now successfully concluded and the DMC recommending study continuation as planned, final study results of this event-driven study are now expected by mid-2014.
###
Notes to Editor:
ABOUT GRIPHON
GRIPHON, (Prostacyclin (PGI2) Receptor agonist in pulmonary arterial hypertension) is a multicenter, double-blind, placebo-controlled trial evaluating the long-term efficacy and safety of oral selexipag in patients with pulmonary arterial hypertension.
GRIPHON is close to full enrollment with 1’143 patients randomized, of the targeted 1’150, and represents the largest randomized, controlled study in PAH patients. This pivotal study is designed to demonstrate a reduction in risk of morbidity/mortality events of selexipag treatment compared to placebo and evaluate the safety of the selexipag in PAH patients. Results are expected to be available mid-2014.
ABOUT SELEXIPAG
Selexipag, originally discovered and synthesized by Nippon Shinyaku, is a first-in-class, potent, orally available, selective IP receptor agonist. Selexipag has major potential as a novel treatment of pulmonary arterial hypertension.[1,2,4]
Results of a Phase II, 43-patient, placebo-controlled, double-blind study, where patients were randomized in a 3:1 ratio receiving selexipag or placebo on top of PDE5 and/or ERA, showed a statistically significant reduction in pulmonary vascular resistance (PVR; primary parameter for the study). The treatment effect was shown to be 30.3% after 17 weeks of treatment (p=0.0045). Results also showed an encouraging numerical improvement in 6-minute walk distance (6MWD), which was a secondary endpoint of this trial. Selexipag was well tolerated and the safety profile was in-line with the expected pharmacologic effect. [3]
ABOUT PULMONARY ARTERIAL HYPERTENSION (PAH)
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The symptoms of PAH are non-specific and can range from mild breathlessness and fatigue during normal daily activity to symptoms of right heart failure and severe restrictions on exercise capacity and ultimately reduced life expectancy.
PAH is one group within the classification of pulmonary hypertension (PH). This group includes idiopathic PAH, heritable PAH and PAH caused by factors which include connective tissue disease, HIV infection and congenital heart disease.
The last decade has seen significant advances in the understanding of the pathophysiology of PAH, which has been paralleled with developments of treatment guidelines and new therapies. Drugs targeting the 3 pathways that have been established in the pathogenesis of PAH are endothelin receptor antagonists (ERAs), prostacyclins and phosphodiesterase-5 inhibitors. PAH treatments have transformed the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago to delayed disease progression today. Improved disease awareness and evidence-based guidelines developed from randomized controlled clinical trial data have highlighted the need for early intervention, goal-oriented treatment and combination therapy.
Despite these advances in PAH, survival rates are unacceptably low and PAH remains incurable.
ABOUT PROSTACYCLIN
Prostacyclin and prostaglandins are types of prostanoids. Endothelial cells produce several vasoactive chemical factors, among them prostacyclin (PGI2), which induce vasodilation of blood vessels and inhibit smooth muscle cell proliferation and platelet aggregation. The peptide endothelin is also produced by the endothelium, and is a potent constrictor of blood vessels and promotes cell proliferation. In a normal healthy state, prostacyclin helps counter-balance the actions of endothelin. In certain disease conditions, however, production of prostacyclin by the endothelium is impaired, allowing the deleterious effects of excessive levels of endothelin to predominate.
ABOUT PROSTACYCLIN RECEPTOR AGONISM
The IP receptor (PGI2 (prostacyclin) receptor) is one of 5 types of prostanoid receptor available to prostanoid replacement therapies. Prostacyclin activates the IP receptor inducing vasodilation and inhibiting proliferation of vascular smooth muscle cells. With selective IP receptor agonism, the risk of side effects mediated by activation of other prostanoid receptors may be minimized.
Actelion is developing a first-in-class, orally available, selective IP receptor agonist that mimics the actions of endogenous prostacyclin for the treatment of PAH.
ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE
Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance in April 2008 to collaborate on selexipag, a first-in-class orally-available, selective IP receptor agonist for patients suffering from pulmonary arterial hypertension (PAH). This compound was originally discovered and synthesized by Nippon Shinyaku. Phase II evaluation has been completed, and a Phase III program in PAH patients has been initiated. Actelion is responsible for global development and commercialization of selexipag outside Japan, while the two companies will co-develop and co-commercialize in Japan. Nippon Shinyaku will receive milestone payments based on development stage and sales milestones as well as royalties on any sales of selexipag.
References
- Kuwano et al. NS-304, an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 2007;322:1181-1188.
- Kuwano et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, NS-304, ameliorates rat pulmonary hypertension with unique relaxant responses of its active form MRE-269 on rat pulmonary artery. J Pharmacol Exp Ther 2008;326:691-699.
- Simonneau G, Lang I, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N. Selexipag, an oral, selective IP receptor agonist for the treatment of pulmonary arterial hypertension Eur Respir J 2012; 40: 874-880
- Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.
NIPPON SHINYAKU
For further information on Nippon Shinyaku please visit:
http://www.nippon-shinyaku.co.jp/english/index.html
ACTELION LTD
Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion’s first drug Tracleer®, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer® through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan, Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium – the single layer of cells separating every blood vessel from the blood stream. Actelion’s over 2,300 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI®).
SOURCE: Actelion
Post Views: 296
